This invention relates to artificial lung surfactants and their use in the treatment of asthma.
It has been estimated that asthma affects between 4 and 10 percent of the population causing distress and alarm to both sufferers and bystanders. Asthma attacks appear to be precipitated in many cases by a number of factors such as exercise or pollutants in the inspired air. Other agents such as pollen and airborne particles may predispose an asthma sufferer to an attack by sensitising the airways. This has led to the belief that effective treatment should include administration of drugs which reduce the sensitivity of asthma sufferers to allergens or which neutralise the allergic reaction.
The present invention is based on a different approach namely that the lungs and airways of non-asthnmatics may contain a natural protective barrier which prevents pollutants and other airborne triggers from reaching receptors whose irritation would then produce an acute attack. While not wishing to be bound by any fixed theory at this stage, studies have suggested that SAPL masks (covers) most of these receptors in normal lungs but this masking is deficient in asthmatics. The present invention is predictated on the belief that it is possible to restore normal masking by binding surface-active phospholipids (SAPL) to the tissue surface of the lungs. thereby reducing the number of receptors exposed to noxious stimuli and reducing hyper-responsiveness of the broncho-constrictor reflex common to all forms of asthma.
SAPL""s are used clinically for the treatment of neonates with respiratory distress syndrome (RDS). In this role. it has been assumed that the SAPL functions by reducing the high surface tension of the air-water interface within the alveoli, thereby reducing the pressure needed to expand the lungs, see Milner, Archives of Diseases in Childhood 1993; 68-253. Thus, commercially available formulations of SAPL have been designed to spread rapidly over an air-aqueous interface, thereby reducing what is otherwise a very high surface tension of water.
Limited clinical studies have been carried out to determine the effect of commercial SAPL""s marketed for treatment of RDS in neonates on asthmatic subjects, xe2x80x94see Kurashima et al. Jap. J. Allergol 1991; 40, 160. This paper reported some amelioration of bronchoconstriction in asthmatic adults using an SAPL obtained by extraction from bovine lungs. In another study on children, also using an SAPL obtained from bovine lungs, no significant changes in lung function or histamine response were found, xe2x80x94see Oetomo et alxe2x80x94American Journal of Respiratory and Critical Care Medicine 153; 1996, page 1148.
Our approach to the problem differs from these studies in that it involves the use of an anti-asthma medicament which is capable of binding (absorbing) to the tissue surface (epithelium) of the airways, thereby masking receptors against stimulation by noxious agents or sensitisation by allergenic stimuli. Although it is an advantage for the medicament employed in this invention to spread over the surfaces of the airways, once in place, one or more components of the composition will migrate across the mucous layer and deposit a thin hydrophobic lining on the tissue surface, and/or supplement the indigenous coating.
According to one of its aspects, the present invention comprises use of a surface active phospholipid (SAPL) composition in the preparation of a medicament for the treatment of asthma by administration of the medicament to the patient""s airways and upper respiratory tract, said medicament comprising SAPL and containing a component capable of binding to the surface of lung tissue.